Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies)

被引:6
|
作者
Laeer, Stephanie [1 ]
Cawello, Willi [1 ]
Burckhardt, Bjoern B. [1 ]
Ablonczy, Laszlo [2 ]
Bajcetic, Milica [3 ]
Breur, Johannes M. P. J. [4 ]
Dalinghaus, Michiel [5 ]
Male, Christoph [6 ]
de Wildt, Saskia N. [7 ,8 ]
Breitkreutz, Joerg [9 ]
Faisal, Muhammed [1 ]
Keatley-Clarke, Anne [10 ]
Klingmann, Ingrid [11 ]
Lagler, Florian B. [12 ]
机构
[1] Heinrich Heine Univ Dusseldorf, Inst Clin Pharm & Pharmacotherapy, D-40225 Dusseldorf, Germany
[2] Goettsegen Gyorgy Hungarian Inst Cardiol HPHC, H-1450 Budapest, Hungary
[3] Univ Belgrade, Sch Med, Univ Children Hosp, Univ Decja Klin UDK, Belgrade 11129, Serbia
[4] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, NL-3584 CX Utrecht, Netherlands
[5] Erasmus MC, Sophia Childrens Hosp, Div Pediat Cardiol, NL-3000 CA Rotterdam, Netherlands
[6] Med Univ Vienna, Dept Paediat & Adolescent Med, A-1090 Vienna, Austria
[7] Erasmus MC, Sophia Childrens Hosp, Intens Care & Dept Pediat Surg, NL-3015 GJ Rotterdam, Netherlands
[8] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Pharmacol & Toxicol, NL-6500 HB Nijmegen, Netherlands
[9] Ethicare GmbH, D-45721 Haltern, Germany
[10] Childrens Heart Federat, London EC2A 3NW, England
[11] Pharmaplex Bvba, B-1970 Wezembeek Oppem, Belgium
[12] Paracelsus Medizin Privatuniv, A-5020 Salzburg, Austria
关键词
pediatric cardiology; heart failure; dilated cardiomyopathy; congenital heart disease; ACEIs; enalapril; orodispersible minitablets; GLOMERULAR-FILTRATION-RATE; PEDIATRIC-PATIENTS; CLINICAL PHARMACOKINETICS; DEVELOPMENTAL-CHANGES; TISSUE DISTRIBUTION; CARBOXYLESTERASE; KIDNEY-FUNCTION; AGE; INFANTS; MODEL;
D O I
10.3390/pharmaceutics14061163
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Angiotensin-converting enzyme inhibitors (ACEI), such as enalapril, are a cornerstone of treatment for pediatric heart failure which is still used off-label. Using a novel age-appropriate formulation of enalapril orodispersible minitablets (ODMTs), phase II/III open-label, multicenter pharmacokinetic (PK) bridging studies were performed in pediatric patients with heart failure due to dilated cardiomyopathy (DCM) and congenital heart disease (CHD) in five participating European countries. Children were treated for 8 weeks with ODMTs according to an age-appropriate dosing schedule. The primary objective was to describe PK parameters (area under the curve (AUC), maximal concentration (Cmax), time to reach maximal concentration (t-max)) of enalapril and its active metabolite enalaprilat. Of 102 patients, 89 patients (n = 26, DCM; n = 63 CHD) were included in the primary PK endpoint analysis. Rate and extent of enalapril and its active metabolite enalaprilat were described and etiology and age could be identified as potential PK modifying factors. The dosing schedule appeared to be tolerated well and did not result in any significant drug-related serious adverse events. The PK analysis and the lack of severe safety events supports the applied age-appropriate dosing schedule for the enalapril ODMTs.
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页数:22
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